Reptiles show remarkable diversity in modes of reproduction and sex determination, including high variation in the morphology of sex chromosomes, ranging from homomorphic to highly heteromorphic. Additionally, the co-existence of genotypic sex determination (GSD) and temperature-dependent sex determination (TSD) within and among sister clades makes this group an attractive model to study and understand the evolution of sex chromosomes. This is particularly so with Lizards (Order Squamata) which, among reptiles, show extraordinary morphological diversity. They also show no particular pattern of sex chromosome degeneration of the kind observed in mammals, birds and or even in snakes. We therefore speculate that sex determination sensu sex chromosome evolution is labile and rapid and largely follows independent trajectories within lizards. Here, we review the current knowledge on the evolution of sex chromosomes in lizards and discuss how sex chromosome evolution within that group differs from other amniote taxa, facilitating unique evolutionary pathways.