Wildlife crime is increasingly gaining prominence in global environmental debates. The crime, generating huge financial returns to few individuals, has far reaching implications on ecology, economy and global security. The seriousness of these implications provides sufficient rationale for reconsidering and intensifying efforts to combat this crime. However, these efforts are compromised by a number of challenges, though opportunities for success exist. This paper presents some of these challenges and opportunities available for reversing the trend of wildlife crime in Tanzania. The challenges presented include poverty, high profit associated with illicit trade on wildlife, poor governance and corruption, minimal budget and inadequate institutional support, political interference and low employee morale, minimal benefits to local communities, human population growth, climate change and HIV/AIDS pandemic. Opportunities identified include increased public awareness, growing global political concern and commitment, presence of relevant policies, programmes and strategies along with international agreements supportive to species protection. Before embarking on challenges and opportunities, the paper provides an overview of Tanzania’s wildlife resources, status and trend of this crime. In conclusion, the paper underscores the gravity of the problem and its implications and offers some recommendations for improving the situation.