Over past decades, nanotechnology has contributed to the biomedical field in areas including detection, diagnosis, and drug delivery via opto-electronic properties or enhancement of biological effects. Though generally considered inert delivery vehicles, a plethora of past and present evidence demonstrates that nanomaterials also exude unique intrinsic biological activity based on composition, shape, and surface functionalization. These intrinsic biological activities, termed self-therapeutic properties, take several forms, including mediation of cell-cell interactions, modulation of interactions between biomolecules, catalytic amplification of biochemical reactions, and alteration of biological signal transduction events. Moreover, study of biomolecule-nanomaterial interactions offers a promising avenue for uncovering the molecular mechanisms of biology and the evolution of disease. In this review, we observe the historical development, synthesis, and characterization of self-therapeutic nanomaterials. Next, we discuss nanomaterial interactions with biological systems, starting with administration and concluding with elimination. Finally, we apply this materials perspective to advances in intrinsic nanotherapies across the biomedical field, from cancer therapy to treatment of microbial infections and tissue regeneration. We conclude with a description of self-therapeutic nanomaterials in clinical trials and share our perspective on the direction of the field in upcoming years.