Uncertainty relations (URs) like the Heisenberg-Robertson or the time-energy UR are often considered to be hallmarks of quantum theory. Here, a simple derivation of these URs is presented based on a single classical inequality from estimation theory, a Cramer-Rao-like bound. The Heisenberg-Robertson UR is then obtained by using the Born rule and the Schrodinger equation. This allows a clear separtion of the probabilistic nature of quantum mechanics from the Hilbert space structure and the dynamical law. It also simplifies the interpretation of the bound. In addition, the Heisenberg-Robertson UR is tightened for mixed states by replacing one variance by the so-called quantum Fisher information. Thermal states of Hamiltonians with evenly-gapped energy levels are shown to saturate the tighter bound for natural choices of the operators. This example is further extended to Gaussian states of a harmonic oscillator. For many-qubit systems, we illustrate the interplay between entanglement and the structure of the operators that saturate the UR with spin-squeezed states and Dicke states.