Over the past several decades, the field of paleopathology has rapidly advanced, but a continuing delay in incorporating scientific advances and a lack of methodological rigor hinder its progress. Inconsistencies in the presentation of data, the persistent use of non‐standardized criteria and non‐specific skeletal lesions to diagnose diseases, and the misuse of or delay in adopting critical, relevant concepts and methods from other disciplines obfuscate the current state of evidence and unnecessarily prolong debates. Here, we present three major research questions that have been affected by these issues: the origin and antiquity of syphilis in the Old World; the pathogen responsible for the Black Death; and whether the incidence of cancer has risen in recent human history. Drawing on these examples, we conclude with recommendations that could facilitate a more rigorous, scientific approach to important questions in paleopathology. Copyright © 2015 John Wiley & Sons, Ltd.