We describe a possible new technique for precise wavelength calibration of high-resolution astronomical spectrographs using femtosecond-pulsed mode-locked lasers controlled by stable oscillators such as atomic clocks. Such ‘frequency combs’ provide a series of narrow modes which are uniformly spaced according to the laser's pulse repetition rate and whose absolute frequencies are known a priori with relative precision better than 10−12. Simulations of frequency comb spectra show that the photon-limited wavelength calibration precision achievable with existing echelle spectrographs should be ∼1 cm s−1 when integrated over a 4000 Å range. Moreover, comb spectra may be used to accurately characterize distortions of the wavelength scale introduced by the spectrograph and detector system. The simulations show that frequency combs with pulse repetition rates of 5–30 GHz are required, given the typical resolving power of existing and possible future echelle spectrographs. Achieving such high repetition rates, together with the desire to produce all comb modes with uniform intensity over the entire optical range, represents the only significant challenges in the design of a practical system. Frequency comb systems may remove wavelength calibration uncertainties from all practical spectroscopic experiments, even those combining data from different telescopes over many decades.