The central focus of the D. E. Shaw group is the pursuit of potentially attractive investment opportunities, and in some cases, the active creation of new ones. Such opportunities form the basis for a number of funds and other investment vehicles, and for the firm's management of assets on behalf of institutional clients. The firm's investment activities may be divided into two broad categories—quantitative strategies based on mathematical and computational models and qualitative strategies based on the analysis of human experts.

The firm deployed its first quantitative strategy soon after its founding in 1988, and is now widely recognized as one of the pioneers of the field of computational finance. Quantitative techniques remain a central focus of the firm's activities, and are used to identify underpriced and overpriced securities, to manage various forms of portfolio risk, and to reduce the cost of transacting in various financial instruments. While a great deal of human effort is expended conducting scientific research in each of these areas, the firm's quantitative strategies are largely based on mathematical models embodied in computer software rather than on human judgments regarding the fundamental soundness of the underlying companies or other assets.

By way of contrast, the firm's qualitative strategies are based on the detailed analysis of particular companies, resources, industries, economies, and entrepreneurial opportunities by experts with extensive asset- and market-specific knowledge. Investments include both publicly traded and privately held financial instruments, certain physical commodities and commercial rights, and in some cases, entire companies. The firm also provides individually tailored debt and equity financing to both healthy and financially distressed companies, makes venture capital investments in early- and later-stage ventures, and organizes and develops new technology-oriented ventures of its own.