We identify a sample of 74 high-redshift quasars (z > 3) with weak emission lines from the Fifth Data Release of the Sloan Digital Sky Survey and present infrared, optical, and radio observations of a subsample of four objects at z > 4. These weak emission-line quasars (WLQs) constitute a prominent tail of the Lya + N v equivalent width distribution, and we compare them to quasars with more typical emission-line properties and to low-redshift active galactic nuclei with weak/absent emission lines, namely BL Lac objects. We find that WLQs exhibit hot (T ~ 1000 K) thermal dust emission and have rest-frame 0.1-5 µm spectral energy distributions that are quite similar to those of normal quasars. The variability, polarization, and radio properties of WLQs are also different from those of BL Lacs, making continuum boosting by a relativistic jet an unlikely physical interpretation. The most probable scenario for WLQs involves broad-line region properties that are physically distinct from those of normal quasars.