In addition to being the critical signal determining muscle contraction, Ca²⁺ has many other important cellular functions. For instance, our laboratory has shown an important role of Ca²⁺ in the insulin-mediated glucose uptake in skeletal muscle cells. Insulin potentiates influx of Ca²⁺ via non-selective cation channels (TRPC3 channels) in both skeletal and cardiac muscle cells. Inhibition of this Ca²⁺ influx results in decreased insulin-mediated glucose uptake in skeletal muscle, whereas increased influx ha the opposite effect. The insulin-mediated Ca²⁺ influx is blunted in both skeletal and cardiac muscle cells of obese, insulin-resistant mice. Moreover, the cellular Ca²⁺ response to electrical stimulation, and hence the contractility, is defective in cardiac muscle cells of obese, insulin resistant mice. The relation between insulin, cellular Ca²⁺ handling and insulin resistance will be discussed.