The phenomenon of antigen processing and presentation and the concept that T cells recognize peptides resulting from the partial catabolism of proteins, are relatively new. These concepts were first recognized and developed at a time when lymphocyte immunity - the adaptive system - and cellular immunity, with its major component of activated macrophages, were not perceived as part of one integrated system. To me, it was the fundamental findings on the role of major histocompatibility (MHC) molecules that set the framework for understanding how phagocytes and the antigen presenting cell (APC) system interact with the adaptive cellular system, in a truly symbiotic relationship (1). In this chapter we make a historical review of the developments that, in my biased opinion, led to the understanding of antigen presentation as a central event. I emphasize my own work, placing it in my perspective of how I saw the field moving.