Technical Abstract: Sex determination depends upon molecular switches that signal whether the male or the female sex-differentiating pathway will be followed during development; it can be triggered by genetic, epigenetic, or environmental cues. Insects display sexual dimorphism, in which males and females differ in form, behavior, and/or physiology. Although sex determination and developmental pathways leading to two distinct sexes are universal within insects, the primary signals that trigger sex determination are highly diverse and differ between groups. The primary signal for sex determination can entail genetic signaling, epigenetic signaling via maternally expressed genes or genomic imprinting of genes, or cytoplasmic factors like B chromosomes and bacterial infections. The primary signals can act alone or in combination. Molecular genetic details of sex determination and sex differentiation are known mainly from Drosophila, and these are further described. Comparison of sex determination of insects, nematode worms, and mammals points to a similar genetic mechanism that underlies sex determination: a cascade of gene expression, with alternative splicing of key genes and intermediate genes, leading to alternative splicing of a double-switch gene that ultimately controls differentiation of males and females. In insects, it appears that key genes and intermediate genes early in the cascade are unique to each group of insects, but genetic pathways for controlling sex differentiation after the double-switch appear to be the same in all insects. Overall, sex determination in insects is highly variable among groups, and in some groups the mechanisms of sex determination differ between populations of a single species.