Microdialysis is commonly used in neuroscience to obtain information about the concentration of substances, including neurotransmitters such as dopamine (DA), in the extracellular space (ECS) of the brain. Measuring DA concentrations in the ECS with in vivo microdialysis and/or voltammetry is a mainstay of investigations into both normal and pathological function of central DA systems. Although both techniques are instrumental in understanding brain chemistry each has its shortcomings. The objective of this review is to characterize some of the tissue and DA differences associated with each technique in vivo. Much of this work will focus on immunohistochemical and microelectrode measurements of DA in the tissue next to the microdialysis probe and mitigating the response to the damage caused by probe implantation.