In this population-based study, we used the SEER database (1985-2015) to examine survival outcomes in chronic lymphocytic leukemia (CLL) patients followed up to the era of advanced treatments including targeted therapies. Data were extracted for patients 15 years or older with a primary diagnosis of CLL. A period analysis was performed to estimate 5- and 10-year relative survival rates for patients diagnosed during different calendar periods from 1985 to 2015. A mixture cure model was used to examine long-term survivors' proportions among patients diagnosed in 1985-2015 and for two cohorts diagnosed in 2000-2003, followed up to 2012 and 2004-2007, and followed up to 2015. Cox proportional hazard modeling was used for the two cohorts to estimate hazard ratios (HRs) of death adjusted for gender and age. The 5-year and 10-year age-adjusted relative survival rate ranged between 73.7 and 89.4% and from 51.6% to "not reached," respectively, for calendar periods of 1985-1989 to 2010-2014. The long-term survivor proportions varied by age and gender from 0 to 59%. The HRs (95%CI) for the 2004-2007 cohort in comparison to the 2000-2003 cohort were 0.58 (0.43-0.78), 0.58 (0.48-0.70), 0.57 (0.49-0.0.67), 0.68 (0.54-0.85), and 0.83 (0.68-1.02) for the age categories of 45-54, 55-64, 65-74, 75-84, and ≥ 85 years, respectively. Overall, relative survival improved significantly for CLL patients diagnosed between 1985 and 2015. These improvements were markedly better following the introduction of targeted therapies.