Biochemical sensors have emerged as a dynamic technique for qualitative and quantitative analysis of different analytes in clinical diagnosis, environmental monitoring, and food and process control. The need for a low-cost, reliable, ultra-sensitive, and rapid sensor continues to grow as the complexity of application areas increases. New biosensing techniques are emerging due to the need for shorter sample preparation protocols. Such novel biosensor designs make field and bed-site clinical testing simpler with substantial decrease in costs per sample throughputs. In this paper, we will review the recent trends and challenges in clinical and environmental biosensors. The review will focus on immunological, nucleic acid, and cell-based clinical and biological sensors. Special emphasis will be placed on the approaches used for immobilization or biological reagents and low-cost electrochemical biosensors. The promising biosensors for rapid diagnosis of cancer or HIV are also discussed.