Human cell lines are commonly used for research investigation. For decades, cell lines have been the workhorse of programs to identify and interrogate mechanisms of action, discover and/or test drug/compounds/ factors, and show relevance of findings to human disease. In this editorial, I pause for thought to reflect on how we should revere the cell lines we use and consider how best and better to incorporate such tools into our research programs. Most laboratories routinely use human cell lines. Many were established decades ago and distributed within the research community. Herein lies the first of our problems. Human cell lines cultures have become so routine that there is a common assumption that cultured lines in one laboratory equal those in another. This is not so. Variations in passage number or culture conditions can result in a drift in the cellular and molecular phenotype; on occasions, cell lines are even misidentified or crosscontaminated. To provide consistency, Endocrine Society editorial policy now requires that all cell lines used and described in all newly submitted and revised manuscripts are authenticated. Effective from January 1, 2015, our policy is similar to guidelines for Nature and American Association for Cancer Research journal publications and concurs with the American Type Culture Collection Standards Development Organization. Providing data on where and when the cells were obtained, if and how they were tested and authenticated, and when they were last tested enables comparison and reproducibility between investigators. Another assumption is that a cell line comprises cells that are equal and similar. In fact, most cells lines are heterogeneous and may include stem/progenitor cells. Although the stem/progenitor cells may be present at low frequency, these cell subpopulations are often the therapeutic target. A global reduction in cell proliferation/ transcription/translation may be 90%–95% and be statistically significant, but the change that is measured may occur only in the differentiated cells that make up the bulk of the cell lines in culture. What about and how do we show alteration to the subpopulations, including stem/progenitors that may constitute a minority of cells? This is a moot point for drug targeting studies, inwhichahighly significant effecton thebulk of the cells is frequently favored compared with any decline in smaller cell subpopulations. Heterogeneity of another type is a further significant issue. Human cell lines are usually obtained from a patient and therefore represent the diseased organ or tissue from that one patient. In 2014 patient variability is a complexity that is acknowledged as being significant. There is a focus on targeted therapies and personalized medicine, but cell lines in culture fail to represent the diversity of patient cohorts. Furthermore, diseases may be chronic, and even in cancer, for example, solid tumors such as breast and prostate cancer develop over years/