Diseases of aging are often complex and multifactorial, involving many genetic and life course modifiers. Systems biology is becoming an essential tool to investigate disease initiation and disease progression. Alzheimer's disease (AD) can be used as a case study to investigate the application of systems biology to complex disease. Here we describe approaches to capturing biological data, representing data in terms of networks and interpreting their meaning in relation to the human population. We highlight issues that remain to be addressed both in terms of modeling disease progression and in relating findings to the current understanding of human disease.