Treatment of ALL in adults is rapidly shifting with the goal of achieving significant improvements in survival rates and reducing toxicities and long-term effects of therapy. The options for treatment vary depending on cytogenetics and molecular genetics. For older adolescents and younger adults up to the age of 40-50 years, the adoption of intensive pediatric treatment regimens has proven to be both feasible and highly effective compared to historical controls with reported 3-5 year survival rates reported in the 70-80% range. The goal of ongoing studies will be to further improve on these rates by introduction of novel agents including antibody conjugates, bi-specific antibodies and small molecule inhibitors to try to enhance early eradication of resistant disease that may lead to relapse. Another goal is further modification of current pediatric backbones to decrease the rate of treatment related toxicities that may reduce the ability to adhere to these aggressive regimens. The concept of reduced intensity treatment with introduction of novel agents into a number of smaller phase II trials is already favorably impacting outcome of our highest risk patients, older adults with Ph- negative ALL. Thus, it is a time of optimism and these treatment strategies, challenges and goals will be reviewed.