Background: Clinical guidelines (CGs) are popular for healthcare decision making but their acceptability and use by healthcare providers is influenced by numerous factors. Some of these factors are professional-related, such as knowledge and perceptions of and attitudes toward CGs in general. The aim of our study was to evaluate attitudes and perceptions of Spanish physicians towards CGs. Methods: We coordinated six discussion groups with a total of 46 physicians. The participants were drawn from 12 medical specialties from both specialized and primary care. We recorded the sessions and transcribed the content verbatim. We analyzed the data using an approach based on the grounded theory. Results: We identified two main constructs that defined the physicians' perceptions towards guidelines: knowledge and usefulness. "Knowledge" defined the theoretical meanings of guidelines, while "Usefulness" referred to the pragmatic approach to guidelines. These constructs were interrelated through a series of categories such as confidence, usability, accessibility, dissemination and formats. Conclusions: In our study, the constructs that impacted most on physician's attitudes to clinical guidelines were knowledge and usefulness. The tension between the theoretical and the pragmatic constructs determined the attitudes and how physicians use guidelines. Groups developing guidelines should ask relevant clinical questions and develop implementable and context specific recommendations. Developers should be explicit and consistent in the development and presentation of recommendations.