Refinement of delivery techniques and sampling in animals used in preclinical studies is among several critical steps in the development of safe and effective therapies such as anti-sense oligonucleotides, and gene therapies. Discovery research requires specialized delivery techniques while IND-enabling toxicology studies transition to standard routes of administration. Tissue collection occurs both during in-life and necropsy. MRI-guided technologies allow delivery into specific areas of the brain, while intrathecal dosing into the spinal cord allows a therapy to reach the cerebrospinal fluid. Examples of specialized delivery methods and sampling in the nonhuman primate model of gene and cell therapy will be provided. This will include historical background information and data gathered in recent years relating to gene therapy.