Atomic force microscopy is a versatile tool for ultrasensitive measurement. We explore the fundamental and practical limits to force sensitivity that are imposed by optical and electrical deflection sensing techniques, and present a method for designing cantilevers to optimize force sensitivity. We calculate the optimized force sensitivity to be1.2×10−18  N/ Hzat a temperature of 4 K, using a gallium arsenide piezoresistive cantilever with dimensionsw=0.1  μm,t=0.1  μm, andL=81  μm, and mechanical quality factorQ=104. The optimized force sensitivities obtained using silicon piezoresistive and optical detection are not far behind.