The first point of a good diagnostic strategy for healthcare-associated pneumonia (HCAP) is correct classification of patients with specific criteria, as suggested by the last American Thoracic Society/ Infectious Diseases Society of America (ATS/IDSA) guidelines. However, clinical practice and recent literature have suggested new risk factors for multidrug-resistant infection (MRI): the presence of permanent indwelling devices, prior antibiotic use in the last 3 months, chronic and advanced pulmonary diseases (chronic obstructive pulmonary disease, bronchiectasis, etc.), history of alcoholism, and immunosuppression. The clinical presentation in HCAP patients is often unusual (mild respiratory symptoms and frequent extrapulmonary manifestations) due to different factors: advanced age, neurological disorders, and multiple chronic comorbidities. Moreover, HCAP commonly presents a worse clinical course than community-acquired pneumonia, a prolonged length of stay, and a mortality rate close to hospital-acquired pneumonia. Chest radiography and routine laboratory markers (including C-reactive protein) are always needed for clinical evaluation and severity assessment. The clinical use of new biomarkers of infection and sepsis (procalcitonin, etc.) is currently being investigated. Extensive microbiological testing to overcome the high prevalence of MRI in HCAP, including urinary antigens for Legionella and Streptococcus pneumoniae; blood cultures; Gram staining and low respiratory tract secretions (sputum, tracheobronchial aspirate, fibrobronchial aspirate, protected specimen brush, bronchoalveolar lavage); and cultures for aerobic, anaerobic, mycobacterial, and fungal pathogens are recommended, whereas the indication for serology tests for respiratory viruses and atypical pathogens is low. By contrast, the new polymerase chain reaction-based techniques for the rapid identification (2 to 4 hours) of microbial pathogens in respiratory samples (nasopharyngeal swab, bronchoalveolar lavage) seem to be the most innovative future perspective in the diagnostics of HCAP.