Antibodies have emerged as powerful therapeutics effective for treating a number of human conditions and diseases. While early successes utilized small animals to generate therapeutic antibodies, human antibodies are now preferred in order to limit anti-antibody immune responses. Antibodies with human amino acid sequences can be generated in a number of ways, such as humanizing antibodies from other species or expressing human antibodies in transgenic animals. This review focuses on methods for obtaining antibodies directly from human B cells. These methods use both antigen exposed and non-exposed (“naïve”) humans as B cell sources, and apply various technologies to isolate desired antibodies; including cell line generation, single cell isolation, display technologies, and B cell library generation.