Researchers searching for alternatives to painful procedures that involve animals may find that the dispersed relevant literature and the array of databases make the search challenging and even onerous. This paper addresses a significant gap that exists for researchers, in identifying appropriate databases to use when searching for specific types of information on alternatives. To facilitate the efficient and effective searching by users, and to ensure compliance with new requirements and improved science, we initiate an evolving guide comprising search grids of database resources organised by animal models and topics (http://www.vetmed.ucdavis.edu/Animal_Alternatives/databaseapproach.html). The search grids present organised lists of specific databases and other resources for each animal model and topic, with live links. The search grids also indicate resources that are freely available worldwide, and those that are proprietary and available only to subscribers. The search grids are divided into two categories: ‘animal models’ and ‘topics’. The category ‘animal models’ comprises: animal model selections; mice; rodents — rats/guinea pigs/hamsters; rabbits; dogs, cats; farm animals, sheep, swine; non-human primates; fish, frogs, aquatic; and exotics. The category ‘topics’ comprises: husbandry; behaviour; euthanasia; toxicity; monoclonal antibodies; teaching; endpoints; disease models; analgesia/anaesthesia; emerging technologies; strategies for specific intervention procedures; and standard operating procedures (for example, drawing blood, behavioural training, transportation, handling, restraint and identification). Users are provided with a selected list of linked resources relevant to their particular search. Starting with an appropriate database that covers the type of information that is being sought is the first step in conducting an effective search that can yield useful information to enhance animal welfare.