In printed electronics, electronic inks are patterned onto flexible substrates using roll-to-roll (R2R) compatible graphic printing methods. For applications where large-area, conformal electronics are necessary, printed electronics holds a competitive advantage over rigid, semiconductor circuitry, which does not scale efficiently to large areas. However, in order to fully realize the true potential of printed electronics, several manufacturing hurdles need to be overcome. Firstly, minimum feature sizes produced by graphic printing methods are typically greater than 25 µm, which is at least an order of magnitude higher for dense, high performing electronics. In this thesis, conductive features down to 1.5 µm are demonstrated using a novel inkjet printing-based process. Secondly, high-resolution printed conductors usually have poor current-carrying capacity, especially for longer wires in large-area applications. This thesis explores the fundamentals of aerosol-jet printing and reveals the regime for printing high-resolution lines with excellent current carrying capacity. Additionally, a novel manufacturing process is demonstrated, which can process 2.5 µm wide conductive wires with linear resistances as small as 5 Ω mm-1. Another challenge for printed electronics manufacturing is to deal with topography produced on the substrate surface by printed features. Besides complicating the subsequent use of contact-printing methods, surface topography is a source of poor device yields as well. This thesis describes two novel methodologies of creating topography-free printed surfaces. In the first method, nanometer-level smooth, planarized silver lines are obtained using a transfer printing approach. In the second method, open microchannels, imprinted in plastic substrates, are filled with a controlled amount of metal using liquid-based additive processes, to obtain conductive wires flush with the substrate surface. Finally, this thesis addresses the issue of overlay alignment, which is the most significant challenge of printed electronics manufacturing. Multi-layered electronic devices require alignment of multiple layers of different materials with micron-level tolerances, which is a daunting task to accomplish on deformable, moving substrates in R2R production formats. This thesis describes a novel, self-aligned manufacturing strategy for printed electronics that relies on capillary flow of inkjet-printed inks within open micro-channels. Multi-level trench networks, pre-engineered on the substrate surface, are sequentially filled with different inks which, upon drying, form stacked layers of electronic materials. Using this approach, fully self-aligned fabrication of all the major building blocks of an integrated circuit is demonstrated. Overall, this thesis presents several new manufacturing avenues for realizing high-performing and dense electronics on plastic by R2R processing.