Alzheimer's disease (AD) is a genetically complex and heterogeneous disorder. Fully penetrant (causal) mutations leading to predominantly early-onset familial AD have been identified in three genes (APP, PSEN1, PSEN2), while for the more common late-onset form of the disease, only one partially penetrant genetic risk factor (APOE) has been established to date. Several lines of evidence suggest that additional susceptibility genes exist for both early- and late-onset AD, however, none of the more than three dozen putative AD loci proposed to date have been consistently replicated in follow-up analyses. Novel AD genes will not only provide valuable clues for the development of novel therapeutic approaches, but will also allow the development of new genetic risk profiling strategies that are an essential prerequisite for early prediction/prevention of this devastating disease. This review focuses on the analytic tools used to identify genes in complex diseases, and then provides a summary of recent linkage and association findings indicating the existence of novel late-onset AD genes on several chromosomes.