Recent research has suggested that the magnitudes of analgesic treatment effects estimated in clinical trials have decreased over time. Implications of these findings for future sample size calculations and clinical trial research designs have not been addressed. In this article, we examine the standardized effect size (SES) for average pain intensity (API) and worst pain intensity (WPI) outcomes from randomized clinical trials (RCTs) of analgesic treatments shown to be efficacious for chronic low back pain, fibromyalgia, osteoarthritis pain, painful diabetic peripheral neuropathy, and postherpetic neuralgia that were published between 1980 and 2016. API and WPI SESs have declined over time and are approximately 0.30 in the most recent trials. This is similar to the mean SESs found in recent RCTs of efficacious antidepressant medications for the treatment of depression. We propose that in many circumstances this value should be considered when conducting sample size determinations for phase 2 and 3 analgesic RCTs. Other methods to address the challenge of modest treatment effects by increasing trial efficiency and assay sensitivity are also briefly discussed. PERSPECTIVE: This article examines continuous pain intensity data obtained from analgesic treatment trials for chronic low back pain, fibromyalgia, osteoarthritis pain, painful diabetic peripheral neuropathy, and postherpetic neuralgia. Numerical declines in standardized effect sizes (SESs) were observed, with SESs being approximately 0.30 in the most recent trials.