Cell-substrate interactions are investigated in a number of studies for drug targets including angiogenesis, arteriosclerosis, chronic inflammatory diseases and carcinogenesis. One characteristic of malignant cancerous cells is their ability to invade tissue. Cell adhesion and cytoskeletal activity have served as valuable indicators for understanding the cancer cell behaviours, such as proliferation, migration and invasion. This review focuses on bio-impedance based measurement for monitoring the behaviours in real time and without using labels. Electric cell-substrate impedance sensing (ECIS) provides rich information about cell-substrate interactions, cell-cell communication and cell adhesion. High sensitivity of the ECIS method allows for observing events down to single-cell level and achieving nanoscale resolution of cell-substrate distances. Recently, its miniaturization and integration with fluorescent detection techniques have been highlighted as a new tool to deliver a high-content platform for anticancer drug development.