Squamata is the largest reptilian order including snakes and lizards which occupies a key position in phylogeny of amniotes. A variety of sex determination modes in lizards is one of the most interesting parts of the biology of this order. These mechanisms are genomic sex determination (both XY and ZW systems) and temperature-dependent sex determination. Studies of squamata sex chromosomes are pivotal for understanding evolution of other vertebrate sex chromosomes. Unfortunately, this clade has long been neglected by molecular geneticists. In this paper, we describe recent data on molecular cytogenetics and genomics of squamates, evolution of their sex chromosomes and sex determination mechanisms.