Research on 2D materials can be traced back to the pioneering work of Langmuir on elemental monolayers in the 1930s [1]. The long-forgotten research area underwent a reawakening with the discovery of graphene, the first two-dimensional atomic crystal, in 2004 [2,3], and its profound success thereafter. Since then, 2D materials such as hexagonal boron nitride, transition metal dichalcogenides, phosphorenes, etc. have been discovered and explored for promising applications [4]. MXenes (pronounced ‘maxenes’) emerged as an elegant member of the above category and soon proved to be versatile enough to revolutionize many aspects of human life by replacing some of the commonly used 2D materials to become the next disruptive technology. MXenes are synthesized from ‘MAX’ phases by the selective etching of ‘A’ layers. The MAX phases are conductive 2D layers of transition metal carbides/nitrides interconnected by the ‘A’ element with strong ionic, metallic, and covalent bonds [5]. As shown in Figure 1, a typical MXene 2D flake is formed by transition elements such as Sc, Ti, V, Cr, Mn, Fe, Y, Zr, Nb, Mo, Hf, Ta, and W interleaved by carbon or nitrogen with the general formula M_n+1X_nT_x, where T_x represents surface functionalities such as F, Cl, O, and OH [6,7,8]. The history of MXenes begins in the year 2011 with the synthesis of 2D-layered Ti₃C₂T_x from the exfoliation of Ti₃AlC₂ MAX phase by Gogotsi‘s group [9]. The initial synthesis approach was conceptualized based on the weak Ti-Al metallic bond. This enabled the easy removal of Al atoms from the Ti₃AlC₂ MAX phase, such as AlF₃, which was later removed by simple washing and resulted in a multilayered, accordion-like structure. This etching process was widely explored for the synthesis of different MXenes, and parameters such as etching time and HF concentration were optimized [10,11]. Owing to the high risk in handling and the corrosive nature of HF, several lower-risk alternative approaches have been conceptualized. Some of these approaches involved chemicals or combinations of chemicals such as NH₄HF₂ [12], HCl/FeF₃ [13], HCl/LiF [14], HCl/NaF [15], HCl/KF [16], HCl/NH₄F/KF [17], and HCl/NH₄F [18], which can act as an in situ source of fluoride ions and improve the safety in operation to a large extent. Nowadays, fluorine-free synthesis approaches are gaining momentum as a new, safer gateway to MXene synthesis, and many innovative top-down synthesis routes, such as electrochemical etching [19,20], thermally assisted electrochemical approaches [21], hydrothermal treatments in NaOH [22] and KOH solutions [23], element replacement by reaction with Lewis acid molten salts [24], salt-templated approaches [25], etc., have been introduced. Moreover, bottom-up synthesis by chemical vapor deposition (CVD), plasma-enhanced pulsed laser deposition (PEPLD), and template methods [26,27] were also reported for the synthesis of MXenes. Because of their 2D planar structure, hydrophilicity, endless and flexible functionalization possibilities, strong absorption in the near-infrared (NIR) region, and exceptional properties, biomedical applications emerged as one of the most promising application fields of MXenes (Scheme 1). MXenes are found to be suitable candidates for applications including anticancer and drug delivery, antimicrobial, photothermal therapy, biosensors, and tissue engineering. However, even with intensive research efforts on MXene, the outstanding properties of these materials alone still cannot meet all the requirements of various biomedical applications. To endow new functions and to improve the performance, MXenes were functionalized, and their surfaces modified. Recently, functional modification of MXenes and the combination of MXenes with 3D [28], 2D [29], 1D [30], 0D [31], and polymer materials [32] with covalent and non-covalent modifications opened a new horizon for the functional requirements of biomedical applications. MXenes were modified with heteroatoms such as sulfur [33], phosphorous [34], and nitrogen [35] to produce functional MXenes. Apart from this, MXenes with enhanced properties were synthesized by doping with boron [36], platinum [37], niobium [38], silicon and germanium [39], vanadium [40], and alkali and alkaline earth metal cations [41]. As an ideal biomaterial for biomedical applications, MXenes, and their composites could be engineered with different physical, mechanical, or chemical properties [42], and must be compatible with the physiological environment with reliable mechanical strength, degradability, and the ability to overcome biological rejection [43]. Even though they have been less explored, several MXenes and their composites have proven to be biocompatible and non-toxic to living organisms [44], and MXenes such as niobium carbide have proven to be biodegradable in mice [45], thereby proving promising for in vivo applications.