Traditional analytic methods are often ill-suited to the evolving world of health care big data characterized by massive volume, complexity, and velocity. In particular, methods are needed that can estimate models efficiently using very large datasets containing healthcare utilization data, clinical data, data from personal devices, and many other sources. Although very large, such datasets can also be quite sparse (e.g., device data may only be available for a small subset of individuals), which creates problems for traditional regression models. Many machine learning methods address such limitations effectively but are still subject to the usual sources of bias that commonly arise in observational studies. Researchers using machine learning methods such as lasso or ridge regression should assess these models using conventional specification tests.