Interest in the cultivation of goldenseal is increasing and this may have benefits for agriculture, human health, and conservation. To enable a better understanding of growing conditions, cultivation methods reported in the literature were reviewed, 21 natural goldenseal populations in the northern portion of its natural range in North America were described and analyzed in terms of population size and health, and 15 successful growers were interviewed on requirements for optimal cultivation. Growing conditions in the wild were compared to those reported in the cultivation literature. Summary of data from natural populations suggests goldenseal grows best in mixed hardwood forests, under 60–65% shade, in moist sandy loam soils high in organic matter, with pH 5.7 to 6.3. Similarly, review of the literature suggests that goldenseal grows best in moist, well-drained loams high in organic matter, with pH 5.5 to 6.5. Reported shade requirements vary but 47–80% shade is considered optimal. Growing conditions reported by growers were also consistent with the cultivation literature and similar to conditions of wild populations. Although optimal growing conditions are similar to those for many crops, goldenseal is relatively robust and can grow well in a variety of conditions including wet, predominantly sandy or clay soils with pH as low as 4.8 and as high as 7.8. Cultivation can utilize a ginseng crop infrastructure and goldenseal has been recommended as a rotation crop for ginseng. Commercial production of goldenseal is potentially advantageous because (1) it is an environmentally friendly crop; (2) it has been grown successfully far outside its natural range, is easy to grow, and is considered potentially profitable; and (3) it is relatively inexpensive, having low energy, land area, and fertilization requirements. Development of a sustainable crop may contribute to the protection of native wild germplasm, which can provide valuable material for crop improvement.