Human endogenous retroviruses (HERVs) and related genetic elements form 504 distinct families and occupy ~8 % of human genome. Modern experimental and bioinformatic techniques in biology made it possible to assess structural and functional impact of HERVs for shaping both the human genome and the molecular machinery of our cells. HERVs encode active retroviral proteins, which may play important roles in human physiology, and may be involved in the progression of cancer and human autoimmune, neurological and infectious diseases. In addition, HERVs regulate expression of the neighboring host genes and modify genomic regulatory landscape, e.g. by providing regulatory modules like transcription factor binding sites (TFBS). Indeed, recent bioinformatic profiling identified ~110,000 regulatory active HERV elements, which formed at least ~320,000 human TFBS. These and other peculiarities of HERVs might have played an important role in human evolution and speciation. In this chapter, we focus on the current progress in understanding of normal and pathological molecular niches of HERVs, on their implications in human evolution, normal physiology and disease. We also review the available databases dealing with various aspects of HERV genetics.