The continuation of the remarkable exponential increases in processing power over the recent past faces imminent challenges due in part rising cost of design and manufacturing and the physics of deep-submicron semiconductor devices. A promising solution to these problems is offered by an alternative to CMOS-based computing, chemically assembled electronic nanotechnology (CAEN). In this talk we discuss the challenges and opportunities posed by CAEN-based computing. We briefly describe recent work in CAEN from the prospective of a computer architecture. The challenges arise from the set of assembly primitives inherent in bottom-up manufacturing. These primitives all but eliminate the ability to create arbitrary connections between devices. The manufacturing methods also imply defect densities which are significantly higher than today's. We show how molecular devices and post-manufacturing reconfiguration can overcome both these obstacles.