The well-posedness theory for hyperbolic systems of first-order quasilinear PDE's with ODE's boundary conditions (on a bounded interval) is discussed. Such systems occur in multi-scale blood flow models, as well as valveless pumping and fluid mechanics. The theory is presented in the setting of Sobolev spaces Hm (m ≥ 3 being an integer), which is an appropriate set-up when it comes to proving existence of smooth solutions using energy estimates. A blow-up criterion is also derived, stating that if the maximal time of existence is finite, then the state leaves every compact subset of the hyperbolicity region, or its first-order derivatives blow-up. Finally, we discuss physical examples which fit in the general framework presented.