Eastern deciduous forests include a remarkable number of plants that are utilized widely for their medicinal properties. However, the long-term sustainable use of medicinal forest plants requires that methods be developed for restoring and cultivating them in natural and semi-natural settings. This study examined the seed regeneration biology of several perennial forest herbs that are internationally traded in the increasingly lucrative botanical medicines industry. Specific objectives were to: (1) determine how environmental cues (temperature, light, substrate, and burial) regulate dormancy-break and carry-over in seed populations of Actaea racemosa (black cohosh), Hydrastis canadensis (goldenseal), and Sanguinaria canadensis (bloodroot); (2) experimentally evaluate seedling recruitment probabilities of A. racemosa, H. canadensis, S. canadensis, and Panax quinquefoliusin different forest microenvironments defined by varying levels of leaf litter and opposing topographic positions; (3) classify seed dormancy and determine optimum germination temperatures for Collinsonia canadensis (stoneroot) and Dioscorea villosa (wild yam); and (4) quantify survival rates and dormancy-levels of A. racemosa and H. canadensis seed populations stored in artificial conditions. Results from these studies showed that: (1) germination probabilities can vary widely when seeds experience different environmental cues, although temperature is the primary factor regulating dormancy-break and germination; (2) some perennial forest herbs can form persistent seed banks and spread germination across time; (3) leaf litter and topographic position can act as ecological filters during early life-history stages; and (4) storing seed populations prior to outplanting reduces viability in H. canadensisseeds and deepens dormancy levels in A. racemosa seed. Recommendations are made for cultivating, managing, and restoring these species in the eastern deciduous forest landscape.