To highlight health related quality of life (HRQOL) measures and published outcomes in phase III clinical trials in the four major cancers: breast, prostate, colorectal, and lung.Peer-reviewed journals, textbooks, and abstracts published between 1990 and 2009.Over the past 20 years there has been an upsurge in the number and types of HRQOL measures used in phase III cancer treatment trials. Results of trials reported after 2001 indicate a significant increase in specific treatment or disease-related symptom measures in lieu of or as companions to global HRQOL measures. Currently, open NCI-supported trials are incorporating a large number of targeted treatment- and/or disease-related measures.Clinicians can use these data to help patients better understand the spectrum and severity of symptomatic toxicities they will experience with cancer treatment.