Since the first report on Ti 3 C 2 T x in 2011, the family of two-dimensional transition metal carbides, nitrides, and carbonitrides (MXenes) has increased substantially to include single and multi-element MXenes, with many more yet to be synthesized but predicted to possess attractive properties. To synthesize these elusive MXenes as well as to improve and scale up the manufacturing of known MXenes, a deeper mechanistic understanding of their synthesis processes is necessary, from the precursors to the etching–exfoliation and final intercalation–delamination steps. Here we examine computational modelling and in situ and ex situ characterization data to rationalize the reactivity and selectivity of MXenes towards various common etching and delamination methods. We discuss the effects of MAX phases, the predominant precursor, and other non-MAX layered materials on MXene synthesis and their resultant properties. Finally, we summarize the parameters behind successful (and unsuccessful) etching and delamination protocols. By highlighting the factors behind each step, we hope to guide the future development of MXenes with improved quality, yield and tunable properties.