The response to treatment and progression of Chronic Obstructive Pulmonary Disease (COPD) varies significantly. Small airways disease (SAD) is being increasingly recognized as a key pathological feature of COPD. Studies have brought forward pathological evidence of small airway damage preceding the development of emphysema and the detection of obstruction using traditional spirometry. In recent years, there has been a renewed interest in the early detection of SAD and this has brought along an increased demand for physiological tests able to identify and quantify SAD. Early detection of SAD allows early targeted therapy and this suggests the potential for altering the course of disease. The aim of this article is to review the evidence available on the physiological testing of small airways. The first half will focus on the role of lung function tests such as maximum mid-expiratory flow, impulse oscillometry and lung clearance index in detecting and quantifying SAD. The role of Computed Tomography (CT) as a radiological biomarker will be discussed as well as the potential of recent CT analysis software to differentiate normal aging of the lungs to pathology. The evidence behind SAD biomarkers sourced from blood as well as biomarkers sourced from sputum and broncho-alveolar lavage (BAL) will be reviewed. This paper focuses on CC-16, sRAGE, PAI-1, MMP-9 and MMP-12.