2014 is the 10th year anniversary of the groundbreaking work on graphene by several pioneering workers. Since then, the field has expanded exponentially and now includes two-dimensional (2D) atomic sheets beyond graphene such as hexagonal boron nitride (hBN), transition metal dichalcogenides (TMDs), and group IV elemental monolayers (e.g. silicene, germanene). While there are many opportunities for these 2D crystals to enable transformational impact, it is widely understood that their greatest prospects are for flexible nanoelectronics where their combined synergistic properties are unmatched by conventional organic or inorganic materials. The 2D atomic sheets have emerged as near ideal nanomaterials to overcome the long running challenge of achieving Si CMOS like performance on soft substrates at scales that can be suitable for large integration. For instance, the high mobility and velocity accessible in monolayer graphene affords GHz analog transistor devices while the large bandgap of graphene’s semiconducting analogues (MoS2 and similar dichalcogenides) naturally lead to near ideal digital transistors with high on/off current ratio and low subthreshold slope while sustaining mobilities much larger than organic semiconductors or amourphous bulk semiconductors. Together, these physically similar atomic layers with vastly different electronic properties can serve as the electronic platform for low-power digital, high-speed mixed-signal, and high-frequency analog transistor building blocks for flexible nanoelectronic systems.In this work, we present the latest findings on the high frequency properties of graphene with record frequencies in the microwave regime. These high frequencies are suitable for realizing GHz wireless analog circuits on soft substrates. The current frequencies are limited by the poor thermal conductivity and reliability of the plastic substrates. In addition, we report on the coupled device mechanics and device physics of 2D semiconducting sheets. The device mechanics on plastic substrate as a function of tensile strain reveal that dielectric cracking is responsible for off-current degradation while buckling is largely responsible for on-current degradation. The buckling scales with the thickness of the dichalcogenide semiconductor and can be mitigated by reducing the driving force for delamination. Optimized dielectric patterning for strain relaxation was found to improve device reliability at low bending radius. Our results collectively indicate that graphene is the most suitable material for flexible radio-frequency transistors while TMDs are ideal for low-power flexible transistors.