Hodgkin lymphomas (HLs) are lymphoid neoplasms uniquely characterized by a paucity of neoplastic cells embedded in a supportive heterogenous cellular microenvironment. Although first described in the 19th century, systematic biological understanding of HLs has been hindered due to the challenges presented in studying the complex tumor microenvironment and scarce tumorigenic cells. Recent advances in single-cell isolation and characterization, sensitive mutational analytic tools, and multiplex immunohistochemical strategies have allowed further advances in understanding the development and progression of HL. Here we provide a current update on the chromosomal and mutational abnormalities seen in HL, the impact of Epstein-Barr virus infection on driving a subset of HLs, and the possibility of disease monitoring via high-sensitivity detection of genetic aberrations. We also discuss recent developments in understanding the intricate microenvironment through intercellular cross-talk, and describe novel potential biomarkers to aid in distinction of HL from other overlapping entities.