In this review, we outline how each cellular lung component participates in the multiple entities that constitute the pathological spectrum of interstitial lung diseases (ILD). It is our intent to highlight the clinically important differential diagnoses. In addition, we discuss the new concepts of the pathogenesis of ILD as they relate to the morphologic presentation of the lung diseases that target the interstitium. The interaction of inflammatory cells such as macrophages, lymphocytes, and mast cells with lung epithelial cells and fibroblasts results in destruction of the lung parenchyma. These cells participate in the disease entities that comprise ILD. They are sources of growth factors and cytokines that allow intercellular communication to occur. Thus, they play a significant role in the process of lung disease.