The quality of the information transfer available utilizing a chronically implanted neural interface likely depends upon the quality of the electrode-tissue interface. High density, high-fidelity neural interfaces require small electrode site areas; unfortunately, these electrodes typically have high initial impedances, as well as exhibit impedance drift post-implant. Here we will discuss our efforts to elucidate and control this electrochemical effect. One mechanism to address initial high-impedance microelectrode interfaces is by applying surface coatings to the metal sites. In this report we quantify the in vitro stability and in vivoperformance of poly(3,4-ethylenedioxythiophene) (PEDOT) and compare with iridium oxide (IrOx) for microstimulation applications. Commercially available neural implants (NeuroNexus) with iridium metal sites were either activated to form IrOx or coated with PEDOT. Biphasic current stimulation was then administered in phosphate buffered saline continuously for two hours at the maximum safe level of charge density determined by Shannon (1992). Prior to stimulation, the PEDOT coated sites displayed lower 1 kHz impedances, higher charge storage capacities and lower amplitude voltage excursions than IrOx sites. After stimulation, PEDOT coated sites displayed no significant change in their impedance, cyclic voltammetry (CV) and voltage excursion measurements, while 1 kHz impedance increased and CVs displayed unstable, pulse-induced activation for the IrOx sites. Typically, regardless of surface modification, chronically implanted neural microelectrodes exhibit increases in impedance magnitude, as well as decreases in the signal-to-noise ratio of electrophysiology. Both of these effects are detrimental for microelectrode-based neuroprosthetic systems. It has been suggested that the reactive tissue response to device implantation may be the main cause of these impedance changes. Previously we have used lumped-circuit element models fit to impedance spectroscopy data to estimate several of these device-tissue interface parameters. Further, we have utilized brief voltage pulses to affect these parameters for a period on the order of hours. One method shown to temporarily mitigate this response and thus improve the interface quality is delivery of a short-duration DC bias voltage to the electrode site (Johnson et al. 2005; Otto et al. 2006). While this method has successfully recovered electrical signals from the interface, other research demonstrates that application of a charge-imbalanced waveform may be harmful to the electrode or electrode-tissue interface. Here, we report the effect of applying charge-balanced sinusoidal AC waveforms on the electrode-tissue interface. We utilized impedance spectroscopy as well as cyclic voltammetry in order to quantify the interface. We use in vitro experiments using 0.9% phosphate buffered saline, varying waveform amplitude, duration, and frequency. In vitro results suggest that, within-limits, charge-balanced waveforms are safer for application of electrical pulses. Subsequent in vivo experiments were conducted using chronically implanted male Long-Evans rats, and cyclic voltammetry, impedance spectroscopy, and electrophysiology measurements were performed.