Tissue macrophages and dendritic cells (DC) are tissue hematopoietic cells that share the ability to sample the environment but have distinct function in tissue immunity. Controversies remain on the best way to distinguish macrophages from DC in vivo. Results in recent months have established that DC derive from a specific hematopoietic lineage in the bone marrow controlled by a unique molecular program distinct from other myeloid programs. Recent results have also established that DC are heterogeneous in origin and function and that dysregulated biology of DC subsets contribute to the pathogenesis of immune disease. The main goal of this Keystone Symposia meeting is to review recent developments in our understanding of basic DC biology and to discuss the relevance of these findings to the pathogenesis of human immune disease. Specifically, we will discuss the mechanisms that control DC differentiation in lymphoid and non-lymphoid tissues during the steady state and diseased state, both at the cellular and transcriptional levels. We will discuss recent developments in our understanding of the molecular control of three unique DC functions that include migration to of the lymph nodes, presentation antigens, and polarization of T cell immune responses. We will debate the role of DC in immune disease – including auto-immunity, inflammation and allergic disease – and address the recent controversy on the role of DC versus basophils in the induction of Th2 response. Specifically, we will discuss the recent discovery of the molecular signature of Langerhans cell histiocytosis, a poorly understood disease that results from the accumulation/proliferation of langerin+ DC. Finally, we will review the relevance of DC in therapy and the basic mechanisms of action of the cell vaccine “Provenge” that has recently been approved by the FDA for the treatment of prostate cancer. The Keystone Symposia meeting on Understanding Dendritic Cell Biology to Improve Human Disease will bring together physicians experts in autoimmune disease, allergy and cancer, immunologists, geneticists, cancer biologists and vaccinologists. We will also invite scientists from the pharmaceutical industry as well as Journal Editors to maximize the interactions between different members of our community and thereby improve our understanding of the key role that DC play in the modulation of human disease and in medicine.