Nurses working in general practice settings are ideally placed to engage with clients who have substance misuse issues, as often they are the first point of contact that clients have in primary care. Working as a primary care nurse with clients with drug dependency issues can be a challenging yet often rewarding experience. Clients with drug dependence often present with complex and multiple health needs and managing these requires the nurse to use problem-solving skills to identify creative solutions to difficult problems. Whilst health promotion and education should always be individualised to clients needs, this is especially important with those who have drug dependency issues. This chapter provides information, guidance and advice for primary care nurses working with clients who have drug dependence.