Aims: The Practical Approach to Lung Health in South Africa (PALSA) initiative aimed to develop an integrated symptom-and sign-based (syndromic) respiratory disease guideline for nurse care practitioners working in primary care in a developing country.Methods: A multidisciplinary team developed the guideline after reviewing local barriers to respiratory health care provision, relevant health care policies, existing respiratory guidelines, and literature. Guideline drafts were evaluated by means of focus group discussions. Existing evidence-based guideline development methodologies were tailored for development of the guideline.Results: A locally-applicable guideline based on syndromic diagnostic algorithms was developed for the management of patients 15 years and older who presented to primary care facilities with cough or difficulty breathing.Conclusions: PALSA has developed a guideline that integrates and presents diagnostic and management recommendations for priority respiratory diseases in adults using a symptom-and sign-based algorithmic guideline for nurses in developing countries.