Idelalisib, ibrutinib, and venetoclax have somewhat different toxicity profiles, and the time-to-event characteristics also tend to vary with the individual drugs. With idelalisib, warnings include fatal and/or severe diarrhea or colitis, hepatotoxicity, pneumonitis, and intestinal perforation. Liver toxicity tends to emerge relatively early, usually occurring within the first 12 weeks of treatment. In contrast, colitis tends to occur later rather than earlier, on the scale of approximately 6 months or more; and pneumonitis is more variable in its time-to-event characteristics. With ibrutinib, many of the toxicities tend to be earlier events, but some, such as hypertension, seem to occur in a percent-per-year–type incidence pattern that does not appear to diminish with time. But, the best approach to understanding these drugs is likely to examine the toxicities individually, and then try to define what the timeline for their emergence may or may not be. With regard to potential toxicities and kinase intolerance, comorbidities can be important with any of the novel agents. In the case of venetoclax, tumor lysis syndrome is a concern, especially in the setting of bulky disease and/or elevated absolute lymphocyte count and reduced renal function.