Cell-cell communication plays an essential role in organismal development and functionality, and communication errors can lead to deleterious effects such as degenerative and autoimmune diseases. However, the intercellular communication network is extremely complex in multicellular organisms making isolation of the functional unit and study of basic mechanisms technically challenging. Despite the level of complexity and many challenges facing researchers in this area, recent development in microfluidic technology allows miniaturized and integrated devices to perform intercellular communication experiments on-chip. Microfluidics have many advantages, including the ability to accurately mimic the chemical, mechanical, and physical cellular microenvironment, precise spatial and temporal control, dynamic characterization, high throughput, scalability and reproducibility. In this Focus article, we highlight some of the recent works and advances in the application of microfluidics to the study of mammalian intercellular communication with particular emphasis on cell contact and soluble factor mediated communication. In addition, we provide some insights into the likely direction of the future developments in this field.