In May 2005, for the third consecutive year, Forbes magazine named Sioux Falls the best small city for business and careers, a ranking based on employment, job and income growth, cost of doing business, labor pool, crime rate, housing costs, and net migration. The Sioux Falls economy is comprised of a diversity of sectors, including finance, healthcare, retailing, agriculture, tourism, and distribution and trade.

When Citicorp moved its credit card operations to Sioux Falls in 1980, it launched the city to new heights in financial services. In the two decades since that time, other financial companies followed, as did those in such related sectors as insurance and real estate. The main offices of state and regional banks, as well as brokerage and insurance firms with nationwide connections, are based in the downtown financial district.

The healthcare industry figures significantly in the citys economic stability. Sioux Falls has emerged as a regional health care center, with the two major hospitals ranking as the top employers in the city, employing roughly 9,000 combined. Private physician clinics employ more than 1,000 workers.