An aging population of humans reflects early-onset morbidity and mortality as well as late-onset disease in the phase when the mortality rate doubles and, finally, longevity of extremely long-lived subjects. Genetic influences have been reported to be relevant for each of these three phases. A growing field in genetic research is aimed at the identification of genes involved in multifactorial diseases of the old and in longevity. Important issues in these studies include the definition of phenotype, which maximally highlights the genetic contribution, whether earlier and later onset phenotypes have loci in common, and how to rank or reject the many candidate disease loci found in different studies. These issues will be illustrated from research on cardiovascular disease and osteoarthritis.