Malignant lymphomas encompass various types of lymphoid neoplasms, possibly originating from cells in various stages of differentiation. The development of high throughput technologies based on knowledge of the human genome identifies novel mutations, epigenetic alterations, and signaling pathways characteristics of each of the lymphoma subtypes. The mutational landscape of tumors may have a clinical impact in terms of identifying rational approaches for molecular target therapy and predictive biomarkers for new therapies. This review will focus on our current understanding of underlying molecular mechanisms, new molecular target drugs, and their activity in lymphomas.