An alternative promoter is a variable region corresponding to initiating transcription of a gene. The use of alternative promoters has led to the diversification of cell types and tissue types and the regulation of complex developmental genes. Aberrant use of alternative promoters plays an important role in the incidence and development of various diseases. As a common mechanism, alternative promoters are versatile and flexible during gene expression regulation. This paper reviewed functional effects of using mammalian alternative promoters, as well as the relationship between alternative promoters and the incidence of diseases based on the latest published studies.