Determining the genetic component of the age-related macular degeneration (AMD) complex trait has been the primary goal of ophthalmic genetics research for almost a decade. During this time, genes of several Mendelian traits affecting the macula have been identified. In this review, we will discuss the consequences of molecular defects in the VMD2, EFEMP1, TIMP3, ELOVL4 and ABCA4 genes, and their association with macular disease. We will also analyze our current knowledge on the implications of genetic variations in these genes for AMD by summarizing data from all studies which have investigated the possible role of these candidate genes in the etiology of AMD. Finally, we will elaborate on methods for genetic dissection of complex traits and discuss the appropriate applications of these methods for identifying genetic determinants of AMD.