Over the past several years, next-generation DNA sequencing technologies are used for the identification of genes responsible for Mendelian disorders and genetic variants related to common disorders. The development of exome sequencing and analysis approaches according to inheritance and pedigree information helps to overcome the majority of limitations encountered by traditional genetic mapping approaches. Different strategies used in previous studies constitute an important source for future studies on genetic disorders. In this review, exome sequencing approaches that are used to identify genetic causes of monogenic disorders and the pros and cons of conventional methods are presented.