Isolated per layer optimization techniques have successfully improved the network performance. However, the increasing number of data-hungry users pressures the designers to rethink the layered OSI architecture and look for cross-layer optimization opportunities to further improve the performance of the network. One of the challenging techniques to get better performance out of the wireless networks is multiple-packet reception (MPR). MPR allows multiple users to share a single time-slot over a frequency band, and hence improves the spectral efficiency of the wireless network. Although there are many MPR designs in the literature, the fact that multiple transmissions are seldom synchronized in a wireless network is ignored in most of these designs. Therefore, in a practical asynchronous network these MPR techniques fail to perform as expected. In this work, we made the realistic asynchrony assumption between the transmission of different nodes to design a practical MPR technique. In our asynchronous design, the structure of the transmitter and the receiver is as simple as the structure of the synchronous counterparts and the performance is almost as good. As mentioned earlier, the barrier between MAC layer and PHY layer breaks when we introduce MPR, and separate design of the two layers becomes impossible. Therefore, we designed MPR-MAC protocols to accompany our MPR techniques in the PHY layer. And the results of our study shows that our cross-layer PHY/MAC design outperforms the existing single packet counterparts. Another solution to improve the performance of a wireless networks is to let the transmitters cooperate to deliver a single message, and in our specific case, let a set of nodes assist a transmitter by relaying its message. Since relaying with multiple relays outperforms relaying using only one relay, it is desirable to have asynchrony insensitive multiple relay schemes. To that end, we introduced an asynchronous distributed space-time coding (DSTC) scheme that works as well as the synchronous counterpart in asynchronous networks. To enable relaying in a random access network, we have designed a relay MAC algorithm that distributively selects the relay nodes and adapts the transmission rates to get the best performance out of the underlying relaying scheme. Our cross-layer PHY/MAC designs are great examples of embracing the asynchronicity in a wireless network and turning it into performance gain.