Randomized controlled trials of veterinary vaccines are essential if we are to have a reasonable understanding of how those vaccines can be expected to perform when used in the field. This manuscript reviews a few (but certainly not all) of the key elements that need to be considered in the design of veterinary vaccine trials. The first step in the design of such a trial is to have a clear statement of the objective of the trial that reflects what is expected of the vaccine (e.g. should it minimize clinical disease or does it need to prevent infection?). Because domestic animals are often managed in groups, the ‘unit of concern’ used in a vaccine trial becomes of great importance. Whether the trial should be carried out at the individual or group level will depend on the objectives of the trial and the extent of concern about ‘group effects’ affecting the trial. Sample sizes will also be influenced heavily by the choice of unit of concern and the nature of the primary outcome being assessed. Finally, while there is no easy solution (except to conduct group-level trials, which may be logistically impossible), the potential for group effects to influence the trial outcome must be considered.