Autonomous reconnaissance missions are called for in extreme environments, as well as in potentially hazardous (e.g., the theatre, disaster-stricken areas, etc.) or inaccessible operational areas (e.g., planetary surfaces, space). Such future missions will require increasing degrees of operational autonomy, especially when following up on transient events. Operational autonomy encompasses: (1) Automatic characterization of operational areas from different vantages (i.e., spaceborne, airborne, surface, subsurface); (2) automatic sensor deployment and data gathering; (3) automatic feature extraction including anomaly detection and region-of-interest identification; (4) automatic target prediction and prioritization; (5) and subsequent automatic (re-)deployment and navigation of robotic agents. This paper reports on progress towards several aspects of autonomous C4ISR systems, including: Caltech-patented and NASA award-winning multi-tiered mission paradigm, robotic platform development (air, ground, water-based), robotic behavior motifs as the building blocks for autonomous tele-commanding, and autonomous decision making based on a Caltech-patented framework comprising sensor-data-fusion (feature-vectors), anomaly detection (clustering and principal component analysis), and target prioritization (hypothetical probing).