Chronic leukemia consists of chronic lymphocytic leukemia (CLL) and chronic myelogenous leukemia (CML). These diseases are generally incurable without hematopoietic stem cell transplant and were previously treated with chemotherapy and immunotherapy. These older therapies have significantly less efficacy and safety than newer targeted therapies. Newer targeted therapies such as BTK inhibitors, Bcl-2 inhibitors, PI3K inhibitors, CAR T cell therapy, and TK inhibitors will be reviewed. This paper will also discuss advances in the diagnosis of these diseases and how we can use modern laboratory techniques to improve risk stratification for both CLL and CML.