Health sentinel networks are being increasingly used in the study of health-related problems. The present article aims to provide a methodological guide - designed by regional sentinel network managers and based on the results of a Delphi study - that can be used to set up and develop a health sentinel network. The main topics in the guide are the following: definition of a health sentinel network; network description: aims and structure; methods for the selection of sentinel participants; description of health processes suitable for study through this methodology: incidence, case definition, exclusion and inclusion criteria; description of the target population: the denominator for incidence rates estimates; quality indicators; periodicity of data collection; dissemination of the information: periodicity and methods, and incorporation of the participants in the decision-making process through multidisciplinary commissions. This guide aims to contribute to the development of sentinel networks in the autonomous communities by providing a common methodology, which could be highly useful when introducing new networks in Spain. Finally, we conclude that it is important to raise awareness of the concept of health sentinel networks, disseminate the information generated, and promote its use by public health administration.