Machine learning offers a set of powerful tools that holds considerable promise for investment management. As with most quantitative applications in finance, the danger of misapplying these techniques can lead to disappointment. One crucial limitation involves data availability. Many of machine learning’s early successes originated in the physical and biological sciences, in which truly vast amounts of data are available. Machine learning applications often require far more data than are available in finance, which is of particular concern in longer-horizon investing. Hence, choosing the right applications before applying the tools is important. In addition, capital markets reflect the actions of people, which may be influenced by others’ actions and by the findings of past research. In many ways, the challenges that affect machine learning are merely a continuation of the long-standing issues researchers have always faced in quantitative finance. While investors need to be cautious—indeed, more cautious than in past applications of quantitative methods—these new tools offer many potential applications in finance. In this article, the authors develop a research protocol that pertains both to the application of machine learning techniques and to quantitative finance in general.