Infectious complications are among the leading causes of mortality in chronic lymphocytic leukemia (CLL). Over the past decade, several advances have been made in treating CLL through inhibition of Bruton tyrosine kinase and the antiapoptotic protein BCL-2. As mortality from CLL progression is expected to decline in the next several years, mortality from severe infections is anticipated to increase. Therefore, understanding the nature of immune defects in CLL and developing strategies to augment the impaired immune system are needed to keep pace with advancements in treatment. This review article summarizes the available data on immune dysfunctions, their clinical consequences, therapeutic implications, and current strategies to enhance immune function in patients with CLL.