The links between wildlife trade regulations and rural livelihoods was researched in three villages in the East Usambara Mountains, northeast Tanzania. The area is unique in terms of its biodiversity, and local communities show a high degree of dependence upon the natural resources for meeting basic livelihood needs (including income generation, health, food and security). The area experiences high levels of wildlife trade to local and international markets, which have been affected by a long history of wildlife trade interventions at local, national and international levels. The various local, national and international trade and access interventions since the mid-1980s has affected the trades in timber, live and dead animals from the East Usambara Mountains, in addition to many other wildlife products. Changes in trade volumes, species composition, price structures and other dynamics are documented. Further, experience from the East Usambara Mountains clearly shows a mixture of positive and negative monetary and non-monetary implications of wildlife access and trade regulations at local, national and international levels. While the positive effects of regulation offset some negative impacts, the overall feeling in the villages studied is one of hardship since the trades started to decline. According to local perceptions, wildlife access and harvest regulations have had a greater overall impact than national and international trade regulations. Evidence suggests that the effect of some trade regulations have actually led to significant positive impacts on local livelihoods, whilst subsequent wildlife access regulations have caused the most negative impacts. Market demand and business acumen are major factors influencing rural peoples’ susceptibility to wildlife access and trade regulation. Finally, the relative importance and weighting of positive and negative livelihood impacts of wildlife access and trade regulations remains a challenging task, and this study discusses a few key issues.